Increased expression of P/Q-type Ca²⁺ channel α_1A subunit mRNA in cerebellum of N-type Ca²⁺ channel α_1B subunit gene-deficient mice

The Ca²⁺ channel α_1B subunit is a pore-forming component capable of generating N-type Ca²⁺ channel activity. Although the N-type Ca²⁺ channel plays a role in a variety of neuronal functions, α_1B-deficient mice show normal behavior, presumably owing to compensation by the other Ca²⁺ channels. In this study, we examined the mRNA expression of the P/Q-type Ca²⁺ channel α_1A subunit in cerebellum of α_1B-deficient mice. The α_1A subunit mRNA in homozygous α_1B- deficient mice was expressed at a significantly higher level than in wild or heterozygous mice. To examine whether the increased expression is induced by a cis-regulatory element within the 5′-upstream region of the α_1A subunit gene, we examined lacZ expression in α_1B-deficient×α_1A3.0-lacZ mice (carrying a 3.0-kb 5′-upstream fragment of the α_1A subunit gene fused to Escherichia coli lacZ reporter gene), which express lacZ in granule but not in Purkinje cells, and in α_1B- deficient×α_1A6.3-lacZ mice (carrying a 6.3-kb 5′-upstream region fused to lacZ gene), which express lacZ in Purkinje but not in granule cells. The levels of lacZ expression in homozygous α_1B-deficient×α_1A3.0-lacZ mice were significantly higher than in wild or heterozygous mice, but no difference in lacZ expression level was found among wild, heterozygous and homozygous α_1B-deficient×α_1A6.3-lacZ mice. Therefore, a possible explanation of the normal behavior of α _1B-deficient mice is that compensation by α_1A subunit gene occurs and that the 3.0-kb 5′-upstream region of α_1A subunit gene contains an enhancer cis-element(s) for compensation in cerebellar granule cells.